Impairment in hand motor function is a major deficit in veterans with cervical spinal cord injury (SCI). While rehabilitative interventions have shown success in improving aspects of hand motor function their overall effects remain limited. The goals of this proposal are to examine the physiology of CNS pathways contributing to the control of hand movements after cervical SCI, and to promote the recovery of hand movements by using non-invasive brain stimulation and motor training. We focus on two basic aspects involved in hand motor function: a precision grip and wrist flexion and extension. These are necessary skills for most of our daily-life activities; therefore, our results may directly impact the quality of life for veterans and their caregivers by enhancing their independence and level of care. We will investigate the contribution of the motor cortex and spinal motoneurons to the control of muscles involved in precision grip and wrist movements after cervical SCI (Aim 1). Transcranial magnetic stimulation (TMS) will be used to examine transmission in corticospinal and intracortical pathways targeting finger and wrist muscles, whereas peripheral nerve stimulation will be used to assess the excitability of finger and wrist motoneurons. These studies will identify the effects of SCI on CNS pathways controlling hand movements. Then, we propose to enhance the recovery of hand motor function by using novel protocols of high frequency non-invasive repetitive TMS (rTMS) and motor training (Aim 2). First, rTMS will be used during precision grip and wrist movements in a task- dependent manner to induce cortical plasticity and enhance voluntary output of hand muscles. Second, rTMS will be applied in a task-dependent manner during a visuo-motor training task that involves precision grip and wrist movements. These unique approaches aim at promoting neuroplasticity during functionally relevant hand movements, which has not been done before. The proposed studies tightly couple basic scientific human research and translational neuroscience. The novel approaches of non-invasive brain stimulation may open new directions for restoring hand motor function after SCI. The absence of well-accepted treatments for hand motor impairments for veterans with cervical SCI and the limited behavioral gains of present interventions underline the importance of these investigations. PUBLIC HEALTH RELEVANCE: Hand motor function is largely disrupted in Veterans with cervical SCI. This has tremendous impact on daily-life activities. This proposal will examine physiological changes in pathways controlling hand motor function after cervical SCI and novel methods to enhance the recovery of hand motor function by combining non-invasive repetitive brain stimulation with motor training. Impairment in hand function is a major problem after stroke, amyotrophic lateral sclerosis, multiple sclerosis, and other motor disorders, therefore, our work may also be relevant for individuals with other lesions of the CNS.